Hepatitis C Virus

Michael S. Forman; Alexandra Valsamakis

doi:10.1128/9781555817381.ch92

Chapter 92 : Hepatitis C Virus

Authors: Michael S. Forman, Alexandra Valsamakis

Content Type: Reference

Publication Year: 2015

Category: Clinical Microbiology

Book DOI: 10.1128/9781555817381

Chapter DOI: 10.1128/9781555817381.ch92

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Abstract:

Hepatitis C virus (HCV) is a flavivirus that is endemic worldwide. Six genotypes are commonly recognized; a seventh rare genotype has been identified. Given its relative prevalence, this chapter focuses on genotypes 1 through 4. HCV is transmitted by blood-borne routes. Most acute infections are asymptomatic and progress to chronicity. Chronic infections are also asymptomatic until significant liver damage occurs. Pegylated alpha interferon plus ribavirin was the only treatment for many years. Highly potent, pan-genotypic, interferon-free direct-acting antiviral (DAA) regimens that cure >95% of clinical-trial subjects have been developed and will dramatically improve treatment. Routine diagnostics include serology, HCV RNA detection/quantification assays, and HCV RNA genotyping assays. Newer diagnostic tests include characterization of host genotype at loci upstream of IL28B that are associated with alpha interferon responsiveness, and HCV RNA tests to detect drug resistance mutations. Serology and HCV RNA detection/quantification tests are useful after a known exposure to identify acute infection. Serology is used to screen for chronic infection; seropositive individuals are then tested with HCV RNA detection/quantification assays to identify chronic infection. HCV genotype and viral load are determined prior to treatment initiation. In the pre-DAA era, HCV genotype was used to predict likelihood of response. It was also helpful to determine treatment regimen and therapeutic duration; these two uses will remain relevant for DAAs. Viral load testing during therapy will likely still be performed for assessment of medication compliance. IL28B genotype may retain some importance in predicting response rates in alpha interferon-containing regimens. Drug resistance tests thus far have limited applicability.

Citation: Forman M, Valsamakis A. 2015. Hepatitis C Virus, p 1599-1616. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch92

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Hepatitis C Virus

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FIGURE 1

HCV genome and protein coding scheme. UTR, untranslated region; E, envelope; NS, nonstructural gene; nuc, nucleotide; pos, position; aa, amino acid; gp, glycoprotein. Numbering is according to references 108 and 109 . doi:10.1128/9781555817381.ch92.f1

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FIGURE 1

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FIGURE 2

Clinical features of acute hepatitis C following exposure to low viral inoculum such as occupational needlestick exposure or community-based exposure ( 49 , 76 , 110 ). Characteristics following higher-dose exposure (transfusion with contaminated blood products) may be different. Intermittent viremia phase estimated from needlestick exposure ( 76 ). Kinetics of other characteristics derived from seroconversion panels ( 49 ). ALT, alanine aminotransferase. Dashed lines indicate potential viremia patterns as defined by HCV RNA levels in peripheral blood. Adapted from reference 49 . doi:10.1128/9781555817381.ch92.f2

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FIGURE 2

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FIGURE 3

Antigens in serology tests currently available commercially in the United States. Abbott HCV EIA 2.0 is the only second-generation screening test currently available. AxSYM, Architect, Ortho 3.0 EIA, Ortho Vitros, and Advia Centaur are third-generation HCV antibody screening tests. HC34, recombinant antigen containing HCV core protein (amino acids [aa] 1 to 150); HC31, recombinant antigen containing NS3 (aa 1192 to 1457) and NS4 (aa 1676 to 1931) separated by an 8-aa linker. c100-3, recombinant antigen containing NS3-4 (aa 1569 to 1931). HCr43, fusion protein of two noncontiguous antigens, c33c and core protein (aa 1 to 150). c200, recombinant antigen containing NS3-4 (aa 1192 to 1931). NS5, recombinant antigen (aa 2054 to 2995). c22-3, recombinant antigen containing core protein (aa 2 to 120). c22p, peptide containing core protein major epitope (aa 10 to 53). doi:10.1128/9781555817381.ch92.f3

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FIGURE 3

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FIGURE 4

Recommended testing algorithm for detection of HCV infection. Derived from reference 111 . doi:10.1128/9781555817381.ch92.f4

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FIGURE 4

Recommended testing algorithm for detection of HCV infection. Derived from reference 111 . doi:10.1128/9781555817381.ch92.f4

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Tables

Hepatitis C Virus

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TABLE 1

Utility of HCV RNA tests in different treatment regimens

TABLE 1

Utility of HCV RNA tests in different treatment regimens

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TABLE 2

Commercial HCV RNA qualitative tests a

TABLE 2

Commercial HCV RNA qualitative tests a

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TABLE 3

Commercial HCV RNA quantification tests a

TABLE 3

Commercial HCV RNA quantification tests a

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TABLE 4

Commercial HCV RNA genotyping tests a

TABLE 4

Commercial HCV RNA genotyping tests a

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TABLE 5

Laboratory-developed HCV RNA genotyping methods a

TABLE 5

Laboratory-developed HCV RNA genotyping methods a

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TABLE 6

Recommendations for chronic hepatitis C screening

TABLE 6

Recommendations for chronic hepatitis C screening

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TABLE 7

Serologic assays for the detection of anti-HCV antibodies a

TABLE 7

Serologic assays for the detection of anti-HCV antibodies a